title: Subcritical CO2 sintering of microspheres of different polymeric materials to fabricate scaffolds for tissue engineering.
abstract: The aim of this study was to use CO2 at sub-critical pressures as a tool to sinter 3D, macroporous, microsphere-based scaffolds for bone and cartilage tissue engineering. Porous scaffolds composed of ~200 μm microspheres of either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) were prepared using dense phase CO2 sintering, which were seeded with rat bone marrow mesenchymal stromal cells (rBMSCs), and exposed to either osteogenic (PLGA, PCL) or chondrogenic (PLGA) conditions for 6 weeks. Under osteogenic conditions, the PLGA constructs produced over an order of magnitude more calcium than the PCL constructs, whereas the PCL constructs had far superior mechanical and structural integrity (125 times stiffer than PLGA constructs) at week 6, along with twice the cell content of the PLGA constructs. Chondrogenic cell performance was limited in PLGA constructs, perhaps as a result of the polymer degradation rate being too high. The current study represents the first long-term culture of CO2-sintered microsphere-based scaffolds, and has established important thermodynamic differences in sintering between the selected formulations of PLGA and PCL, with the former requiring adjustment of pressure only, and the latter requiring the adjustment of both pressure and temperature. Based on more straightforward sintering conditions and more favorable cell performance, PLGA may be the material of choice for microspheres in a CO2 sintering application, although a different PLGA formulation with the encapsulation of growth factors, extracellular matrix-derived nanoparticles, and/or buffers in the microspheres may be advantageous for achieving a more superior cell performance than observed here.
authors.affiliation: Bioengineering Graduate Program, University of Kansas, Lawrence, KS, USA.
authors.forename: Manjari
authors.initials: M
authors.lastname: Bhamidipati
authors.forename: BanuPriya
authors.initials: B
authors.lastname: Sridharan
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Scurto
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D006025:Glycosaminoglycans / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D002245:Carbon Dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006909:Hydroxyproline; D002118:Calcium
keywords: Microspheres; PCL; PLGA; Sintering; Subcritical CO(2)